The purpose of this study is to determine the safety and efficacy of the mTOR inhibitor sirolimus as a treatment for renal angiomyolipomas in patients with tyberous sclerosis complex or sporadic lymphangioleiomyomatosis.

Inherited mutations of the TSC1 or TSC2 gene cause tuberous sclerosis while acquired (somatic) mutations of either gene are associated with sporadic lymphangioleiomyomatosis (LAM). Renal angiomyolipomas are a feature of both disorders. TSC1 and TSC2 regulate signalling through the mammalian target of rapamycin (mTOR) pathway. Inhibition of mTOR may result in a decrease in size of TSC 1/2 assciated lesions. We are treating patients with tuberous sclerosis or sporadic LAM with the mTOR inhibitor rapamycin in a non-randomised, open label pilot study of safety and efficacy. Change in size of renal angiomyolipomas is the primary end point

Eligibility

Ages Eligible for Study:

18 Years to 65 Years (Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

If female, documentation of negative pregnancy test prior to enrolment.

Participants, including males, must use an effective form of contraception, whilst taking sirolimus and for twelve weeks after stopping the drug

One or more renal angiomyolipomata of at least two centimetres or greater in largest diameter

In those who have had a renal haemorrhage, known conservatively managed renal aneurysm(s) greater than 10mm

Patients who have had embolisation for AML(s) within the preceding 6 months

Patients who are unable to walk 100 metres on the flat

Continuous requirement for supplemental oxygen

Patients who have had or are being considered for organ transplant

Uncontrolled hyperlipidaemia

Intercurrent infection at initiation of Sirolimus

Surgery within last 2 months

Pregnant or lactating women

Use of an investigational drug within the last 30 days

Change in anti epileptic drug medication within the last 3 months

Likely to need vaccination e.g. for travel during the course of the trial (except for influenza vaccine in patients with LAM)

Current usage of strong inhibitors of CYP3AE ( such as ketoconazole, voriconazole, itraconazole, tilithromycin or clarithromycin) or strong inducers (such as rifampicin or rifabutin)

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00490789